At the University of Washington Primate Research Center (WPRC), several macaque species show an acquired immunodeficiency syndrome (simian AIDS, SAIDS) characterized by lymphocytopenia, opportunistic infections, and a retroperitoneal fibromatosis tumor (RF). Numerous type D retroviruses, designated SAIDS-D/W, have been isolated by cocultivation of tissues and blood with lymphocyte and monolayer cultures. These SAIDS-D/W isolates can be distinguished from all other type D retroviruses by antigenicity and restriction enzyme pattern. Another retrovirus has been isolated on the HuT 78 cell line after cocultivation of a lymph node from a Macaca nemestrina that had died with lymphoma in 1982 at the WPRC. This isolate, designated MnIV (WPRC-1) (M. nemestrina immunodeficiency virus), shows the characteristic morphology of a lentivirus and replicates to high titers in various human and primate lymphocyte lines. The relatedness of MnIV to other lentiviruses (HTLV-III/LAV, EIAV, visna) was examined immunologically and by N-terminal amino acid sequence analysis of the major viral gag protein. Fourteen of the 24 N-terminal residues of MnIV p28 and HTLV-III/LAV p24 are identical. These results indicate that MnIV belongs to the same lentivirus family as HTLV-III/LAV, but is only partially related to these human AIDS retroviruses. SAIDS-D/W and MnIV have been inoculated into several primate species; the former virus causes RF tumors and the latter results in severe immunosuppression. A retrovirus isolated from an AIDS patient and designated human immunodeficiency virus, Frederick isolate 3 (HIV(FRE-3)) has a defect in processing of the gag precursor protein and produces immature virus particles. The virus is being biologically cloned on sheep choroid plexus cells and will be molecularly cloned in order to study the biochemical basis of the defect.